title: Enhanced expression of hepatic acyl-coenzyme A synthetase and microsomal triglyceride transfer protein messenger RNAs in the obese and hypertriglyceridemic rat with visceral fat accumulation.
abstract: The liver plays a central role in lipoprotein metabolism. In particular, very-low density lipoprotein (VLDL) is assembled in the hepatocytes and secreted into the blood circulation. The VLDL is then catabolized to low-density lipoprotein by lipoprotein lipase and hepatic triglyceride lipase. Obese subjects, especially those with visceral fat accumulation, are frequently associated with hyperlipidemia, non-insulin-dependent diabetes mellitus (NIDDM), and hypertension. The mechanism of hyperlipidemia in visceral fat obesity has not yet been elucidated. Otsuka Long-Evans Tokushima Fatty (OLETF) rat is an animal model of NIDDM, characterized by obesity with visceral fat accumulation, hyperlipidemia, and late-onset insulin resistance. To elucidate the mechanism of hyperlipidemia observed in OLETF rats, we focused on the production of VLDL by the liver and investigated hepatic messenger RNA (mRNA) levels of microsomal triglyceride transfer protein (MTP), acyl-coenzyme A synthetase (ACS), and apolipoprotein B (apo B), which play important roles in VLDL synthesis and secretion. In 6-week-old OLETF rats, in which insulin resistance had not been manifested, visceral fat weight was already higher and portal free fatty acid (FFA) and VLDL-triglyceride levels were elevated compared with the control rats. Hepatic ACS activity and mRNA levels, and MTP mRNA levels were also increased in OLETF rats, whereas apo B mRNA levels were similar; these results suggest that the enhanced expression of both ACS and MTP genes associated with visceral fat accumulation before developing insulin resistance may be involved in the pathogenesis of hyperlipidemia in obese animal models with NIDDM.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kuriyama
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: I
authors.initials: I
authors.lastname: Shimomura
authors.forename: T
authors.initials: T
authors.lastname: Funahashi
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: K
authors.initials: K
authors.lastname: Aragane
authors.forename: K
authors.initials: K
authors.lastname: Miyaoka
authors.forename: T
authors.initials: T
authors.lastname: Nakamura
authors.forename: K
authors.initials: K
authors.lastname: Takemura
authors.forename: Z
authors.initials: Z
authors.lastname: Man
authors.forename: K
authors.initials: K
authors.lastname: Toide
authors.forename: N
authors.initials: N
authors.lastname: Nakayama
authors.forename: Y
authors.initials: Y
authors.lastname: Fukuda
authors.forename: M C
authors.initials: MC
authors.lastname: Lin
authors.forename: J R
authors.initials: JR
authors.lastname: Wetterau
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000273:Adipose Tissue / Q000033:anatomy & histology; D000367:Age Factors; D000818:Animals; D001054:Apolipoproteins A / Q000378:metabolism; D001835:Body Weight; D002352:Carrier Proteins / Q000378:metabolism*; D003066:Coenzyme A Ligases / Q000378:metabolism*; D015228:Hypertriglyceridemia / Q000378:metabolism*; D008079:Lipoproteins, VLDL / Q000032:analysis; D008297:Male; D009765:Obesity / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D011922:Rats, Mutant Strains; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides / Q000032:analysis; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: D001054:Apolipoproteins A; D002352:Carrier Proteins; D008079:Lipoproteins, VLDL; D012333:RNA, Messenger; D012097:Repressor Proteins; D029701:Saccharomyces cerevisiae Proteins; D014280:Triglycerides; C106092:microsomal triglyceride transfer protein; D003066:Coenzyme A Ligases; C090799:FAA2 protein, S cerevisiae; D000098859:Long-Chain-Fatty-Acid-CoA Ligase